1. Field of the Invention
This invention is directed to a process for coupling an amino acid or derivative thereof to digitoxigenin, digoxigenin or a derivative of either.
2. Description of the Prior Art
Amino acids or derivatives thereof have been coupled to digitoxigenin or digoxigenin utilizing isobutylchloroformate, pivaloyl chloride or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. See for example U.S. Pat. No. 3,855,208 and Oliver et al. J. Chem. Inv. Vol. 47, pages 1035 - 1042 (1968).
However, when tyrosine methyl ester is coupled to 12 acetyl-3-succinyl-digoxigenin utilizing pivaloyl chloride to affect coupling, the reaction must be run at low temperatures and under anhydrous conditions in order to achieve acceptable yields. Furthermore, the desired reaction product must be usually isolated from a complex reaction mixture.
An improved process for coupling amino acids or derivatives thereof to digitoxin or digoxigenin would, therefore, be an advancement in the art.